Mass spectrometry (MS) is an analytical methodology used for quantitative elemental analysis of samples. Molecules in a sample are ionized and separated by a spectrometer based on their respective masses. The separated analyte ions are then detected and a mass spectrum of the sample is produced. The mass spectrum provides information about the masses and in some cases the quantities of the various analyte particles that make up the sample. In particular, mass spectrometry can be used to determine the molecular weights of molecules and molecular fragments within an analyte. Additionally, mass spectrometry can identify components within the analyte based on a fragmentation pattern.
Analyte ions for analysis by mass spectrometry may be produced by any of a variety of ionization systems. For example, Atmospheric Pressure Matrix Assisted Laser Desorption Ionization (AP-MALDI), Atmospheric Pressure Photoionization (APPI), Electrospray Ionization (ESI), Atmospheric Pressure Chemical Ionization (APCI) and Inductively Coupled Plasma (ICP) systems may be employed to produce ions in a mass spectrometry system. Many of these systems generate ions at or near atmospheric pressure (760 Torr). Once generated, the analyte ions must be introduced or sampled into a mass spectrometer. Typically, the analyzer section of a mass spectrometer is maintained at high vacuum levels from 10−4 Torr to 10−8 Torr. In practice, sampling the ions includes transporting the analyte ions in the form of a narrowly confined ion beam from the ion source to the high vacuum mass spectrometer chamber by way of one or more intermediate vacuum chambers. Each of the intermediate vacuum chambers is maintained at a vacuum level between that of the proceeding and following chambers. Therefore, the ion beam transports the analyte ions and transitions in a stepwise manner from the pressure levels associated with ion formation to those of the mass spectrometer. In most applications, it is desirable to transport ions through each of the various chambers of a mass spectrometer system without significant ion loss. Often an ion guide is used to move ions in a defined direction in the MS system.
Ion guides typically use electromagnetic fields to confine the ions radially while allowing or promoting ion transport axially. One type of ion guide generates a multipole field by application of a time-dependent voltage, which is often in the radio frequency (RF) spectrum. These so-called RF multipole ion guides have found a variety of applications in transferring ions between parts of MS systems, as well as components of ion traps. Often, ion guides are also operated in presence of a buffer gas to reduce the velocity of ions in both axial and radial directions. This reduction in ion velocity in the axial and radial directions is known as “thermalizing” or “cooling” the ion populations due to multiple collisions of ions with neutral molecules of the buffer gas, and the resultant transfer of kinetic energy. Thermalized beams that are compressed in the radial direction are useful in improving ion transmission through orifices of the MS system and reducing radial velocity spread in time-of-flight (TOF) instruments. RF multipole ion guides create a pseudo potential well, which confines ions inside the ion guide.
Beam limiting apertures are used to limit transverse spatial width and angular spread (beam divergence) of the ion beam. Limiting the spatial width and angular spread of the ion beam is useful because ion trajectories, which deviate too much from the beam axis in either transverse position or angular heading, can lead to a dispersion in the mass analyzer. This dispersion in the mass analyzer is based on ion initial conditions rather than purely on ion mass. For example, in an “ideal” TOF MS system, the ion time of flight only depends on the ion mass, since that is the quantity to be measured. In reality, time of flight depends weakly on the exact spatial location and angular heading of each ion. The spread of positions and angular deviations causes a spread in time of flight and reduces the mass resolution of the TOF MS system. Consequently, in many mass analyzers the beam size and angular spread are limited with a set of two consecutive apertures in a field free region, sometimes referred to as a slicer, which prevents ions outside the acceptable range from entering the analyzer.
While beam limiting apertures are useful in improving precision in mass measurements, known MS systems that incorporate beam limiting apertures in the ion guide have certain drawbacks. First, beam limiting apertures reduce the overall mass spectrometer sensitivity by preventing a significant portion of the ion beam from entering the mass analyzer. Second, ions that are incident on the metal surface comprising the beam limiting aperture can contaminate the metal surface over time and distort the electrostatic fields in the vicinity. This field distortion can alter the ion beam direction, which can degrade mass resolution and sensitivity, cause the system to be unstable, and block the beam all together.
To minimize the effects of these problems associated with the known slicer, it is desirable to condition the ion beam so that a large portion of the ion beam will pass through the apertures. In known MS systems, a series of electrostatic lenses focuses the ion beam for optimal coupling through the apertures of the slicer. However, in known MS systems, even with optimal coupling, transmission through the slicer is limited by the beam emittance, which is defined as the product beam spatial size and angular spread. This fundamental limitation is a direct consequence of the conservation of phase space density. Reducing the beam emittance as much as possible is therefore desirable. Beam brightness, which is defined as the ion beam current divided by the beam emittance, is desirably increased by reducing the beam emittance. However, known ion guides do not suitably confine low beam emittance.
In a known gas buffer device, ions reach approximate thermal equilibrium with the buffer gas and then are subsequently accelerated to at least several electron volts of axial energy after leaving the gas filled region. The final emittance has two contributions, angular spread and spatial spread, both of which are influenced by the buffer gas cooling process in the ion guide. In the limiting case, the final angular spread is given simply by the ratio of the thermal velocity to axial velocity, a quantity known as the thermal angular spread. Practical devices get close to the thermal spread at room temperature. In known ion guides, reducing the angular spread further requires costly refrigeration of the buffer gas and consequently is rarely pursued in mass spectrometry.
In addition, as noted above many mass spectrometer ion sources function more efficiently at comparatively high ambient pressures (e.g., near 1 atm (760 Torr)). By contrast, most mass spectrometers function at significantly lower pressures. For example, the pressures maintained inside the MS vacuum chamber are from 10−4 Torr to 10−8 Torr. Transferring ions from the ion source to the chamber using many known techniques results in significant losses of ions.
While ion guides, such as known multipole ion guides, are useful in guiding ions in MS systems, these known ion guides are not practical for use at comparatively high pressures (e.g., near atmospheric temperatures). Specifically, at comparatively low pressures ion confinement using known ion RF multipole ion guides is acceptable. However, ion confinement and guidance using known ion guides becomes unacceptable at pressures above a certain pressure that is well below the suitable pressure for the ion source.
Two common problems limit the maximum functional pressure for known ion guides. First, the length scales, or the distance between the electrodes of known ion guides, are too great and as a result the pressure at which electrostatic breakdown occurs is unacceptably low. Moreover, at higher pressures, the RF power required to effect suitable ion confinement can be too great for practical implementation.
What is needed, therefore, is an apparatus that overcomes at least the shortcomings of known structures described above.